Randomised, split‐face study of a dermocosmetic cream containing Sphingobioma xenophaga extract and Neurosensine® in subjects with rosacea associated with erythema and sensitive skin

Abstract Introduction Rosacea is a chronic inflammatory skin condition associated with erythema, inflammation and skin sensitivity. Objectives To assess the benefit of a dermocosmetic cream (DC cream) containing Sphingobioma xenophaga extract and soothing agent in adult females with rosacea‐associated erythema and sensitive skin. Materials and Methods During phase 1, DC was applied twice daily on the randomized half‐face and compared to usual‐skincare (USC) for 28 days. During phase 2, DC was applied on the full face twice daily for 56 days. Clinical, instrumental and skin sensitivity assessments were performed at all visits; demodex density (standardized skin surface biopsy (SSSB) method) was performed at baseline and D28, quality of life (QoL) was assessed using the stigmatization questionnaire (SQ), Rosacea Quality of Life index (ROSAQoL) and Dermatology Life Quality Index (DLQI) at baseline and D84. Results At D28, a significant benefit of DC over USC was observed for erythema, tightness, burning and stinging (all p ≤ 0.05), erythema measured by chromameter (p < 0.01), corneometry and transepidermal water loss (p < 0.0001 and p < 0.05, respectively), skin sensitivity (p < 0.001) and significant reduction of mean demodex density (p < 0.05) on the DC side. At D84, DC significantly (all p < 0.05) improved clinical signs and symptoms on both sides of the face compared to baseline; SQ, ROSAQoL and DLQI scores improved by 40.4%, 25.0% and 55.7%, respectively compared to baseline. Tolerance was excellent. Conclusion DC significantly improved erythema, skin sensitivity, demodex count, QoL and feeling of stigmatization of subjects with rosacea and is very well tolerated.


INTRODUCTION
Rosacea is a chronic inflammatory skin condition.It is commonly associated with an altered skin barrier, a dysbalanced microbiome, inflammation and vasodilation. 1Persistent erythema and telangiectasia are frequent primary features, and can be associated with flushing and papules, as well as sensitive skin symptoms. 2,3The course of rosacea is fluctuant, with periods of flares and remission. 4 subjects with rosacea, the skin barrier is damaged and more sensitive towards external aggressions such as heat, cold and pollution. 7,80][11] Symptoms of sensitive skin are frequently reported in rosacea and include skin burning, itching, stinging and tingling.
Moreover, patients often feel uncomfortable and stigmatized, adding a psychosocial burden to the visible features of rosacea. 2,3Several of these symptoms have been described as the secondary symptoms of rosacea. 1 Rosacea is associated with a microbiome dysbiosis with increase in Demodex mites and expression of transient receptor potential cation channel subfamily V member 1 TRPV1, tropomyosin receptor kinase A (TrkA) and nerve growth factor (NGF), triggering cutaneous neurogenic inflammation. 5Rosacea associated with erythema and flushing and burning sensation refractory to traditional treatment may be designated as neurogenic rosacea. 6specific dermocosmetic cream (DC cream, Toleriane Rosaliac ® AR concentrate cream, La Roche-Posay Laboratoire Dermatologique, France) containing acetyl dipeptide-1 cetyl ester (Neurosensine ® ), a soothing compound that acts on skin sensitivity by decreasing erythema and irritation as well as reducing signs related to neurogenic inflammation, and shea butter to moisturise the skin barrier, has been developed for rosacea patients.12 It also contains an extract of a flagellated bacterial strain of Sphingomonas xenophaga isolated from the endogenous flora component of La Roche-Posay thermal spring water.
It improves skin barrier function, decreases inflammation and inhibits, with a dose-response effect, the activity of pre-Kallikrein which plays an important role in inflammation. 13The increase in quantity and the magnitude of biological activity of Kallikrein 5 leads to the increased production of cathelicidins such as LL-37.LL-37 is an antimicrobial peptide that increases innate cutaneous inflammation, vasodilation and vascular proliferation, which are underlying pathogenic features of rosacea. 14is study assessed the benefit and local tolerance of DC cream in patients with rosacea associated with erythema and sensitive skin.

MATERIALS AND METHODS
This, randomized, controlled, double phase (phase 1: split-face, phase were recruited. 15ring phase 1 and according to a randomisation schema, subjects applied DC cream on one half-face and their commercially purchased usual skin care on the other half-face (USC) twice daily, in the morning and evening, for 28 days.This comparative and randomised period was followed by a 56-day period during which all subjects applied DC cream twice daily on the full face, up to visit D84.Demodex density was assessed at Baseline and Day 28 on both sides of the face using the standardized skin surface biopsy (SSSB) method; microscopy pictures were taken using Dinolite ® AM, Dunwell Tech, USA with DinoCapture ® 2.0 software. 16[19] Global tolerance was assessed at all post-baseline visits on a scale from 0 = none to 3 = excellent tolerability.
Mean values, standard deviations and variations were calculated.

DISCUSSION
Results from this study conducted in women with almost clear or mild rosacea associated with erythema, and sensitive skin showed that the tested dermocosmetic cream compared to the patients' usual skin care significantly (all p < 0.05) improved erythema, rosacea signs and symptoms as well as skin sensitivity as early as after 15 days of daily use.
Moreover, when switching after 28 days from USC to the DC cream, clinical and instrumental assessments confirmed that the DC cream was able to rapidly improve the condition of the half-face previously having received the USC while continuing in parallel to improve the half-face previously treated with the DC cream.
In rosacea, the natural skin barrier is damaged and neurogenic inflammation is activated. 20Dermocosmetics combined with a topical treatment or applied as a maintenance regimen are useful for subjects with rosacea, as they help to improve clinical signs and symptoms. 21e present study did not only show that the tested DC cream improved clinical signs and symptoms of rosacea compared to routine skin care, but also significantly (p < 0.05) improved physical skin barrier parameters, objective redness measured by chromametry, and reduced the density of Demodex after 28 days of daily use, thus helping to restore skin homeostasis.These improvements contributed to a significantly improved QoL and perception of social stigmatization, as shown after 84 days, thus confirming the added value of the tested DC cream compared to routine skin care in the management of very mild to mild rosacea.
The small sample size may be considered a limitation.However, due to the intra-individual study design, the sample size of 42 hemi-faces may be considered as sufficient to assess the benefits of the DC cream in rosacea compared to the subjects' usual skin care regimen.
In conclusion, in the present study in subjects with rosacea associated with erythema and skin sensitivity, DC cream containing S.
xenophaga extract and Neurosensine ® significantly improved signs and symptoms, regulated skin hydration and reduced the Demodex density compared to standard skin care.Moreover, the DC cream improved the subjects' QoL and perception of social stigmatization and was very well tolerated.
The ANOVA and the Bonferroni Tests were used to compare instrumental data at baseline, D15, D28 and D84.The t-test was used to compare variations at D15-baseline, D28-baseline and D84-baseline in the DC cream-treated areas and in those having received USC.The Friedman ANOVA and Kendall's Concordance Coefficient Scores were used to compare clinical evaluations and the stinging test at baseline, D15, D28 and D84.The Wilcoxon test for non-parametric and dependent data was used to compare variations at D15-baseline, D28baseline, D84-baseline and the Demodex density on both half-face sides, as well as for the scores of stigmatization, DLQI and RosaQoL questionnaire at baseline and D84.